XPC-6444 is a potent, isoform-selective, CNS-permeable (penetrable) inhibitor of NaV1.6 (IC50=41 nM for hNaV1.6). XPC-6444 also effectively blocks NaV1.2 (IC50=125 nM). XPC-6444 has anticonvulsant (antiepileptic/antiseizure) activity.

Physicochemical Properties

Molecular Formula	C22H25F3N4O2S2
Molecular Weight	498.584712743759
Exact Mass	498.137
CAS #	2230144-21-3
PubChem CID	134585831
Appearance	Off-white to yellow solid powder
LogP	4.4
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	9
Heavy Atom Count	33
Complexity	722
Defined Atom Stereocenter Count	0
SMILES	S(C1=C(C=C(C=C1F)NCC1C(=CC=CC=1CN(C)C(C)(C)C)F)F)(NC1=CSC=N1)(=O)=O
InChi Key	VOJFVKGTRNXOTJ-UHFFFAOYSA-N
InChi Code	InChI=1S/C22H25F3N4O2S2/c1-22(2,3)29(4)11-14-6-5-7-17(23)16(14)10-26-15-8-18(24)21(19(25)9-15)33(30,31)28-20-12-32-13-27-20/h5-9,12-13,26,28H,10-11H2,1-4H3
Chemical Name	4-[[2-[[tert-butyl(methyl)amino]methyl]-6-fluorophenyl]methylamino]-2,6-difluoro-N-(1,3-thiazol-4-yl)benzenesulfonamide
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	IC50: 41 nM (hNaV1.6), 125 nM (hNaV1.2)[1]
ln Vitro	High selectivity over NaV1.1 and NaV1.5 is demonstrated by XPC-6444[1].
ln Vivo	In human liver microsomes and hepatocytes, XPC-6444 demonstrates strong metabolic stability and a modest propensity for MDR1-mediated efflux[1].
References	[1]. Identification of CNS-Penetrant Aryl Sulfonamides as Isoform-Selective NaV1.6 Inhibitors with Efficacy in Mouse Models of Epilepsy. J Med Chem. 2019 Oct 3.

Solubility Data

Solubility (In Vitro)

DMSO: 125 mg/mL (250.71 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.17 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.17 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.0057 mL	10.0285 mL	20.0570 mL
	5 mM	0.4011 mL	2.0057 mL	4.0114 mL
	10 mM	0.2006 mL	1.0028 mL	2.0057 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.